National Cancer Institute

at the National Institutes of Health

Intraocular (Uveal) Melanoma Treatment (PDQ®)

Health Professional Version

Table of Contents

General Information About Intraocular (Uveal) Melanoma Treatment

Incidence and Mortality

Melanoma of the uveal tract (iris, ciliary body, and choroid), though rare, is the most common primary intraocular malignancy in adults. The mean age-adjusted incidence of uveal melanoma in the United States is approximately 4.3 new cases per million people, with no clear variation by latitude. Males have a higher incidence than females (4.9 vs. 3.7 per million).[1] The age-adjusted incidence of this cancer has remained stable since at least the early 1970s.[1,2] U.S. incidence rates are low compared with the rates of other reporting countries, which vary from about 5.3 to 10.9 cases per million. Some of the variation may be the result of differences in inclusion criteria and methods of calculation.[1]

Uveal melanoma is diagnosed mostly at older ages, with a progressively rising, age-specific, incidence rate that peaks near the age of 70 years.[3]

Host susceptibility factors associated with the development of this cancer include:[2-4]

Caucasian race.

Light eye color.

Fair skin.

The ability to tan.

In view of these susceptibility factors, numerous observational studies have attempted to explore the relationship between sunlight exposure and risk of uveal melanoma. To date, these studies have found only weak associations or yielded contradictory results.[3] Similarly, there is no consistent evidence that occupational exposure to UV light or other agents is a risk factor for uveal melanoma.[3,5]

Anatomic Location

Uveal melanomas can arise in the anterior (iris) or the posterior (ciliary body or choroid) uveal tract. Iris melanomas have the best prognosis, whereas melanomas of the ciliary body have the least favorable prognosis.[6] Most uveal tract melanomas originate in the choroid. The ciliary body is less commonly a site of origin, and the iris is the least common. The comparatively low incidence of iris melanomas has been attributed to the characteristic features of these tumors, i.e., they tend to be small, slow growing, and relatively dormant in comparison with their posterior counterparts. Iris melanomas rarely metastasize.[7] Melanomas of the posterior uveal tract generally have a more malignant, histologic appearance; are detected later; and metastasize more frequently than iris melanomas. The typical choroidal melanoma is a brown, elevated, dome-shaped subretinal mass. The degree of pigmentation ranges from dark brown to totally amelanotic.

Diagnosis

Careful examination by an experienced clinician remains the most important test to establish the presence of intraocular melanoma. It is not possible to distinguish a small uveal melanoma from a nevus. Small uveal lesions are often observed for growth to make a diagnosis of melanoma. Clinical findings that may help to identify melanoma include:[6]

Tumor thickness of more than 2 mm.

Subretinal fluid.

Visual symptoms.

Orange pigment on the tumor surface.

A tumor margin touching the optic disc.

Ancillary diagnostic testing, including fluorescein angiography and ultrasonography, can be extremely valuable in establishing and/or confirming the diagnosis.[9] In a large, retrospective, single-center series of 2,514 consecutive patients with choroidal nevi, the progression rates to melanoma at 5, 10, and 15 years were 8.6%, 12.8%, and 17.3%, respectively.[10]

Prognostic Factors

A number of factors influence prognosis. The most important factors include the following:

Several additional microscopic features can affect the prognosis of intraocular melanoma, including:

Mitotic activity.

Lymphocytic infiltration.

Fibrovascular loops (possibly).

Cell type is the most commonly used predictor of outcome following enucleation, with spindle-A cell melanomas carrying the best prognosis and epithelioid cell melanomas carrying the least favorable prognosis.[1,4,9] Nevertheless, most tumors have an admixture of cell types, and there is no clear consensus regarding the proportion of epithelioid cells that constitutes designation of a tumor as mixed or epithelioid.[6]

Extraocular extension, recurrence, and metastasis are associated with an extremely poor prognosis, and long-term survival cannot be expected.[11] The 5-year mortality rate associated with metastasis from ciliary body or choroidal melanoma is approximately 30%, compared with a rate of 2% to 3% for iris melanomas.[12]

Classification and Stage Information for Intraocular (Uveal) Melanoma

Tumor Size

Uveal melanoma most often assumes a nodular or dome-shaped configuration, but occasionally tumors can be flat or diffuse and involve extensive areas of the uvea with little elevation.

Tumor size classifications according to boundary lines used in a Collaborative Ocular Melanoma Study (COMS) are as follows:[1]

Small: Range from 1.0 mm to 3.0 mm in apical height and largest basal diameter of 5.0 to 16.0 mm.[1]

Medium: Range from 3.1 to 8.0 mm in apical height and a basal diameter of not more than 16.0 mm.[2]

Large: Greater than 8.0 mm in apical height or a basal diameter more than 16.0 mm, when the apical height is at least 2.0 mm.

Although most ocular melanomas have a raised configuration, about 5% grow in a diffuse pattern that also may have prognostic significance. The tumors have a horizontal, flat-growth pattern, with the thickness measuring approximately 20% or less than the greatest basal dimension. This uncommon variant of uveal melanoma seems to have a poorer prognosis, particularly when the diameter is large, and the margins are poorly defined.[3]

In clinical practice, the tumor base may be estimated in average optic disc diameters (1 dd = 1.5 mm). The average elevation may be estimated in diopters (3 diopters = 1 mm). Other techniques, such as ultrasonography, should be used to provide more accurate measurements.

An important function of ophthalmic ultrasonography is the detection of extrascleral extension.[4,5] Extrascleral extension measuring 2 mm or more in thickness can be demonstrated provided it is located behind the equator where the intraocular tumor, sclera, and adjacent orbital fat are readily imaged.[6] Orbital extraocular extension of choroidal melanoma may be found in eyes with medium and large tumors, but it is very rare in eyes with small melanomas.

Metastatic Disease

Systemic metastases are evident in only 1% to 4% of patients at the time of diagnosis of the primary ocular melanoma.[7] Because the uveal tract is a vascular structure without lymphatic channels, tumor spread occurs principally by local extension and by dissemination through the blood stream. Lymphatic spread is rare but may occur after local extension into the conjunctiva and its lymphatics.[8] Given the rarity of nodal metastases, sentinel node biopsies of nonclinically involved nodes are not done as part of the staging procedure.[7]

Systemic metastases are generally hematogenous in origin, and the first site identified is usually the liver.[9] Lung, bone, and subcutaneous sites are also common.[9] In the COMS trials, the liver was the only site of detectable metastasis in 46% of patients with metastases reported during follow-up or at the time of death; 43% had metastases diagnosed in the liver and other sites.[9] In patients with a history of ocular melanoma who present with hepatic metastases of unknown origin, metastatic melanoma should be considered in the differential diagnosis.

It is particularly unusual for choroidal melanomas of any size to invade the optic nerve or its meninges.[10] Metastasis of choroidal melanoma to the contralateral choroid is also rare.[9,11]

Staging

Definitions of TNM

An American Joint Committee on Cancer staging system has been developed for melanoma of the uveal tract.[7]

bThese definitions apply to both clinical and pathologic staging.[12] Note: In clinical practice, the largest tumor basal diameter may be estimated in optic disc diameters (dd, average: 1 dd = 1.5 mm). Tumor thickness may be estimated in diopters (average: 2.5 diopters = 1 mm). However, techniques such as ultrasonography and fundus photography are used to provide more accurate measurements. Ciliary body involvement can be evaluated by the slit-lamp, ophthalmoscopy, gonioscopy, and transillumination. However, high-frequency ultrasonography (ultrasound biomicroscopy) is used for more accurate assessment. Extension through the sclera is evaluated visually before and during surgery, and with ultrasonography, computed tomography, or magnetic resonance imaging. Note: When histopathologic measurements are recorded after fixation, tumor diameter and thickness may be underestimated because of tissue shrinkage.

cIris melanomas originate from, and are predominantly located in, this region of the uvea. If less than half of the tumor volume is located within the iris, the tumor may have originated in the ciliary body and consideration should be given to classifying it accordingly.

dPrimary ciliary body and choroidal melanomas are classified according to four tumor-size categories.

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

Irisc

T1

Tumor limited to the iris.

T1a

Tumor limited to the iris not more than 3 clock hours in size.

T1b

Tumor limited to the iris more than 3 clock hours in size.

T1c

Tumor limited to the iris with secondary glaucoma.

T2

Tumor confluent with or extending into the ciliary body, choroid, or both.

T2a

Tumor confluent with or extending into the ciliary body, choroid, or both, with secondary glaucoma.

T3

Tumor confluent with or extending into the ciliary body, choroid, or both, with scleral extension.

T3a

Tumor confluent with or extending into the ciliary body, choroid, or both, with scleral extension and secondary glaucoma.

Treatment Option Overview

Role of Observation

Iris melanomas have relatively good outcomes with a 5-year survival rate of more than 95%. They are predominantly of the spindle-cell type and are usually smaller in size than posterior melanomas because of earlier detection. Conservative management is generally advocated whenever possible, but surgical intervention may be justified with unequivocal tumor growth or with extensive disease at initial examination.

The management of small choroidal melanomas is controversial, and it is not clear whether treatment of small tumors prevents metastasis.[1] The natural history of small choroidal melanoma is poorly understood. Small, pigmented, choroidal lesions cannot always be differentiated reliably on examination. Growth is a presumed indicator of malignant potential.[2] The likelihood of progression from the time of diagnosis to the time when tumor growth warrants treatment has not been well characterized. Some ophthalmologists advocate observation. This has been justified on several grounds, including the difficulty with establishing a correct diagnosis, the lack of any documented efficacy for globe-conserving treatments, and concerns for severe treatment-related morbidity. Others have advocated earlier therapeutic intervention.[1,3,4]

Although patients diagnosed with small choroidal tumors were not eligible for participation in the Collaborative Ocular Melanoma Study (COMS), these patients were offered participation in a prospective follow-up study to evaluate the natural history of small lesions. Two-year and 5-year tumor growth estimates of 21% and 31%, respectively, were reported.[5] Clinical risk factors associated with tumor growth included:[3,5]

Increased tumor thickness.

Presence of subretinal fluid.

Orange pigmentation.

Absence of drusen.

Absence of retinal pigment.

Margin at the optic disc.

Epithelial changes surrounding the tumor.

Role of Surgery

The selection of treatment depends on the following:

Site of origin (choroid, ciliary body, or iris).

Size and location of the lesion.

Age of the patient.

Occurrence of extraocular invasion, recurrence, or metastasis.

Enucleation

In the past, enucleation (eye removal) was the standard treatment for primary choroidal melanoma, and it is still used for large tumors. However, enucleation has been largely replaced by radiation therapy (i.e., brachytherapy with radioactive plaques; or external-beam, charged-particle radiation therapy) to spare the affected eye.[6,7]

Pre-enucleation external beam radiation therapy (EBRT)

In the case of large, choroidal tumors judged to require enucleation, the role of pre-enucleation EBRT was tested in a randomized trial and had no impact on overall survival (OS).[8,9][Level of evidence: 1iiA] In a COMS trial, 1,003 patients with large choroidal melanomas (≥2 mm in height and ≥16 mm in diameter, or ≥10 mm in height irrespective of diameter, or ≥8 mm in height and border <2 mm from the optic disc) with no known metastases were randomly assigned to receive enucleation alone or after preoperative external photon-beam radiation from cobalt 60 or accelerators (20 Gy in five daily fractions) to the orbit and globe.[8,9] Through 10 years of follow-up, the median survival in both arms was approximately 7 years, and the 10-year all-cause mortality was 61% in both arms (relative risk for death of 1.00; 95% CI, 0.85–1.18). Metastasis-free survival was also virtually identical in both arms.

Transscleral local resection

Eye-sparing transscleral local resection plays a very limited role in the management of uveal melanoma. It is used in patients with large choroidal and ciliary body tumors who are not candidates for radiation therapy but are highly motivated to retain their eye.[10-12] The procedure is technically demanding and is generally performed only in centers with specialized expertise in this surgery. There is a substantial risk of retinal detachment, intraocular bleeding, and complications associated with the anesthesia-induced hypotension used to decrease the risk of bleeding. Adjuvant brachytherapy or neoadjuvant proton-beam therapy is often administered. Experience is limited to retrospective, single-center, case series.[10-12][Level of evidence: 3iiiDiv]

Surgical resection of metastases

Surgical resection of metastases from ocular melanoma has been reported in case series of highly selected patients with occasional favorable outcomes.[13,14] However, the favorable outcomes may be the result of strong patient-selection factors, and the role of resection in this setting is unclear.[13,14][Level of evidence: 3iiiDiv]

Role of Radiation Therapy

Episcleral brachytherapy using plaques containing small radioactive “seeds” is the most common form of radiation used in the management of intraocular melanoma. Iodine-125 (125I), cobalt-60 (60Co), palladium-103 (103Pd), iridium-192 (192Ir) and ruthenium-106 (106Ru) are examples of radioactive isotopes used in the brachytherapy plaques. Isotopes with relatively low photon and electron emissions (125I, 103Pd, and 106Ru) are more easily shielded to reduce the exposure to adjacent normal tissues, and 125I is probably the most commonly used radioisotope.[15] Although plaque radiation therapy allows preservation of the eye, visual acuity is frequently lost over time.

In a case series of 1,106 patients who were treated with plaque radiation therapy for uveal melanoma and who had an initial acuity of at least 20/100, 68% developed poor acuity (i.e., 20/200 or worse) within 10 years.[16]

Factors associated with worse acuity outcomes included the following:[16]

Age older than 60 years.

Diminished baseline acuity.

Diabetes.

Increased tumor size and thickness.

Location near the fovea or optic disc.

isotope (106Ru, 60Co, or 192Ir vs. 125I).

125I brachytherapy yields equivalent overall and melanoma metastasis-specific survival rates to enucleation for medium-sized melanomas.[17][Level of evidence: 1iiA] The randomized COMS Medium Tumor Trial compared 125I episcleral-plaque brachytherapy (85 Gy at 0.42–1.06 Gy/hr) to enucleation in 1,317 patients with medium-sized choroidal tumors (tumor height 2.5 mm–10.0 mm and tumor diameter ≤16.0 mm that were not contiguous with the optic disc).[17] Eighty-five percent of the patients treated with 125I brachytherapy retained their eye for 5 years or more, and 37% of them had visual acuity better than 20/200 in the irradiated eye 5 years after treatment.[17] No statistically significant differences in mortality were observed between the two study arms after 12 years of follow-up, whether considering death from all causes or death with histopathologically confirmed melanoma metastasis.[18] Five- and 10-year all-cause mortality rates were 19% and 35% in both study arms; cumulative all-cause mortality at 12 years was 43% in the 125I arm versus 41% in the enucleation arm (RR, 1.04; 95% CI, 0.86–1.24). Five-year metastasis-specific mortality rates were 13% in both arms; at 10 years, the rates were 21% and 22% (RR for metastasis-specific mortality, 1.07; 95% CI, 0.81–1.41 through 12 years).

In a companion study within the COMS, 209 patients were prospectively assessed for quality of life during the first 5 years of follow-up.[19] Both study groups reported increasing difficulty with vision-oriented daily activities and ocular pain as time elapsed. Most measures of visual function were similar between the two groups, but there were statistically significant differences favoring the brachytherapy group in comfort with driving for the first year after therapy and in reported peripheral vision for the first two years after therapy. These differences disappeared by year 5 of follow-up.[19][Level of evidence: 1iiC]

Charged-particle EBRT (using protons, carbon ions, or helium ions) is the other major form of radiation therapy used in the management of ocular melanomas.[20-23] This form of radiation therapy requires sophisticated equipment available only at selected centers, and charged-particle EBRT involves patient cooperation during treatment (e.g., voluntarily fixating the eye on a particular point so the tumor is positioned properly in the radiation beam). A lower risk of early and late local radiation failures has been reported after charged-particle EBRT than after brachytherapy, possibly resulting from differences in dose distribution of the two techniques.[20][Levels of evidence: 1iiDiv and 3iiiDiv]

In a single-center, single-surgeon study 184 patients with uveal melanomas smaller than 15 mm in diameter and smaller than 10 mm in thickness were randomly assigned to receive 125I brachytherapy versus helium ion radiation (to an estimated dose of 70 Gy equivalents in five fractions over 7 to 11 days in each arm).[24] The local tumor regrowth rate by 4 years was 13.3% in the brachytherapy arm versus 0% in the helium ion arm (P < .001). However, the rates of metastasis, death from metastasis, and overall mortality was very similar in both arms.[24][Level of evidence: 1iiDiv]

Because of its dose distribution, charged-particle irradiation can be used to treat larger tumors and tumors closer to the fovea or optic disc than plaque brachytherapy. A large, single-center, single-surgeon series of 2,069 patients treated with proton-beam therapy had an actuarial local control rate of 95% (95% CI, 93%–96%) at 15 years. The cumulative rate of enucleation was 16% (95% CI, 13%–20%), most frequently as a result of neovascular glaucoma, blind uncomfortable eyes, or local recurrence (46%, 31%, and 23% of enucleations). As with plaque radiation, risk factors for deterioration in visual acuity after charged-particle radiation were tumor size, location near the fovea or optic disc, baseline acuity, and underlying diabetes.[21]

Similarly, another large, single-center, single-surgeon, consecutive series of 886 patients treated with proton-beam irradiation reported a local control rate of 92.1% (95% CI, 89.8%–94.6%) and ocular conservation rate of 87.3% (95% CI, 83.9%–90.9%) at 10 years.[22]][Level of evidence: 3iiDiv] The actuarial OS at 10 years was 64.1% (95% CI, 59.5%–69.0%).

In a single-center, phase I/II study of 57 evaluable patients treated with carbon ion-beam irradiation and followed for a median of 26 months, 26 patients developed neovascular glaucoma or severe eye pain from increased intraocular pressure, and 3 patients had enucleation. One patient had a local tumor recurrence.[23]

In an attempt to lower the complication rate and improve functional outcome, a decreased dose of 50 cobalt Gy equivalents (CGE) has been compared to 70 CGE proton beam (each delivered in 5 fractions, usually within a 7-day period). Patients (n = 188) with tumors smaller than 15 mm in diameter and smaller than 5 mm in height that were located near the optic disc or macula were randomly assigned to the two doses in a double-masked study design. At 5 years, there were no statistically significant differences in local tumor control, rate of metastasis, visual acuity, or complication rates. However, the visual fields were better in the 50 CGE group.[25][Level of evidence: 1iDiv]

As noted above in the section on the Role of Surgery in the Treatment Option Overview section of this summary, the role of pre-enucleation external photon-beam radiation therapy has been tested in a randomized trial and has shown no impact on OS for large choroidal tumors treated with enucleation.[8,9]

External-beam–photon-beam (gamma-ray) radiation therapy with gamma-knife stereotactic radiation surgery as a single-fraction [26] or fractionated stereotactic radiation [27,28] is being investigated as an alternative to brachytherapy or charged-beam radiation for posterior uveal melanomas, particularly for tumors too large or too close to the optic disc or macula to treat with brachytherapy. Because the dose rate of radiation delivery is slower than is the case with charged particles, specialized techniques are used to immobilize the eye [26] or to avoid delivery of the photons while the eye is moving or closed.[28] Experience is more limited with external-beam–photon therapy than for either brachytherapy or charged-particle EBRT, and there are no controlled comparisons to either of the other techniques. Early results from single-center series suggest similar levels of local tumor control and eye retention rates, but patient-selection factors may play a role.[28][Level of evidence: 3iiiDiv]

Role of Transpupillary Thermotherapy

Transpupillary thermotherapy (TTT) directs an infrared laser, usually at a wavelength of 810 nm, through a dilated pupil in one or more sessions to induce heat necrosis of uveal melanomas. This method carries the theoretical advantage of high-precision destruction of tumor tissue under direct visualization. However, TTT has important limitations that confine its use to very restricted circumstances.[1,29] The limited ability of TTT to penetrate thick tumors with sufficient energy restricts its use to small melanomas, or tumors of a size that some ophthalmologists recommend for follow-up without any initial therapy. (Refer to the Role of Observation section in the Treatment Option Overview section of this summary for more information.) When used as the primary therapy, there are relatively high rates of local recurrence and retinal vascular damage. Recurrence rates are particularly high when the tumor abuts the optic nerve and overhangs the optic disc.[1][Level of evidence: 3iiiDiv]

In a single-center study, 95 patients with small choroidal melanomas (diameter <10 mm and thickness <3.5 mm) were randomly assigned to TTT versus 125I brachytherapy (100 Gy).[30] The tumor regression rates in the TTT and 125I arms were 92% and 98%, respectively (P = .4). With a mean follow-up time of 56.2 months, there were four recurrences in the TTT arm and one in the 125I arm. However, the study is too small to provide clear information on efficacy differences.

TTT is also under evaluation as an adjunct to primary therapy with proton-beam radiation. In the setting of large uveal melanomas, proton-beam therapy is associated with exudative, inflammatory, and glaucomatous complications that may require enucleation. In a single-center trial, 151 patients with uveal melanomas at least 7 mm thick or at least 15 mm in diameter were randomly assigned to receive proton-beam radiation (60 CGEs over four daily fractions) with or without TTT (810 nm wavelength at 1, 6, and 12 months after therapy) and followed for a median of 38 months.[31] There were no differences between the two groups in maculopathy, papillopathy, or glaucoma. The enucleation rate was lower in the TTT group (about 2% vs. 18% at 5 years, P = .02). However, the study was not masked, and replication would be important.

There are uncertainties regarding the optimal management of intraocular melanoma at all stages. Physicians should discuss with eligible patients opportunities for entry into ongoing clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

Iris Melanoma

Melanocytic stromal proliferations and nevi of the iris are the most common tumors of the iris, but melanoma is rare.[1,2] Clinical differentiation between an iris nevus and a melanoma might sometimes be difficult and at times may be impossible. Melanomas of the iris are usually small discrete lesions, although they may occasionally be diffuse, infiltrative, or multiple and may result in heterochromia, chronic uveitis, or spontaneous hemorrhage into the anterior chamber of the eye (hyphema). Iris melanomas that involve more than 66% of the angle circumference are associated with secondary glaucoma.[3]

Routine evaluation of iris melanomas includes gonioscopy, transillumination of the globe, and indirect ophthalmoscopy with 360° of scleral depression. Photographic documentation is essential to document progression in size or growth of the tumor.[4] Anterior segment fluorescein angiography may be helpful to demonstrate the vascularity of the lesion but is not diagnostic. High-resolution ultrasound biomicroscopy can be used to measure small lesions (basal dimensions and thickness) and to assess tumor involvement of the anterior ciliary body, angle, and overlying sclera.[5] The main disadvantage with this technology is its limited penetration of large lesions. In these cases, conventional ultrasonography is more accurate.

In general, iris melanomas have relatively good outcomes. Only about 3% of these melanomas develop metastases within 5 years.[1] Iris melanomas are predominantly of the spindle-cell type and are usually smaller in size than posterior melanomas. Clinical features, including prominent tumor vascularity, rapid growth, and heterogeneous pigmentation, are associated with an epithelioid cell component.[6] Involvement of the iridocorneal angles is frequently associated with ciliary body invasion.[6]

Given their rarity and good prognosis, trials with sufficient power are practical. Therefore, treatment experience is based principally on case series and case reports. Conservative management is generally advocated whenever possible, but surgical intervention may be justified with unequivocal tumor growth and with extensive disease at initial examination.

Local resection: When progressive and pronounced growth is documented.[2]

Enucleation: If the tumor is not amenable to local resection (diffuse involvement of the iris, involvement of more than 50% of the iris and anterior chamber angle, intractable glaucoma, and extraocular extension).[7]

Plaque radiation therapy: Offered as an alternative for large, diffuse, surgically nonresectable lesions of the iris.[8]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with iris melanoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Ciliary Body Melanoma

Melanoma involving the ciliary body is a rare tumor that carries a poor prognosis. In some cases, diagnosis may be difficult because of similarity to other eye diseases. The differential diagnosis of ciliary body melanoma should be considered in cases of unilateral pigmentary glaucoma and chronic uveitis.[1]

Ultrasound biomicroscopy can be used to evaluate tumor shape, thickness, margins, reflectivity, and local invasion.[2,3] Patients with tumors greater than 7 mm in thickness are at increased risk for metastatic disease and melanoma-related death compared with patients with thinner tumors.[4]

Standard treatment options:

There are several options for management of ciliary body melanoma. All of them are reported from case series.[Level of evidence: 3iiiDiv] The choice of therapy, however, depends on many factors.

Plaque radiation therapy: Local control rates are high, but treatment is associated with a high incidence of secondary cataract.[4,5]

Local tumor resection: This option is mainly suitable for selected ciliary body or anterior choroidal tumors with smaller basal dimension and greater thickness.[9,10]

Enucleation: This option is generally reserved for large melanomas when there is no hope of regaining useful vision. It is also indicated in the presence of intractable secondary glaucoma and extraocular extension.[5,8]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with ciliary body and choroid melanoma, small size. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Small Choroidal Melanoma

A wide range of 5-year mortality rates have been reported among patients treated for small choroidal melanomas, with an average rate of about 16%.[1,2] Several studies indicate that the two most important clinical factors predictive of mortality are larger tumor size (at the time of treatment) and documentation of tumor growth.[3]

The management of small choroidal melanomas is controversial. The likelihood of progression from the time of diagnosis to growth warranting treatment has not been well characterized. Many ophthalmologists advocate initial observation. This initial management strategy is justified on several grounds, including the difficulty in establishing a correct diagnosis, the lack of any documented efficacy for globe-conserving treatments, and concerns for severe treatment-related morbidity. Others have advocated earlier therapeutic intervention.[4-6]

Standard treatment options:

Observation: This strategy is important for patients with an uncertain diagnosis or in whom tumor growth has not been documented. It is also used for asymptomatic patients with stable lesions (particularly elderly or debilitated patients), and patients with a tumor in their only useful eye.[2]

Plaque radiation therapy: This treatment is used for small- or medium-sized uveal melanomas, amelanotic tumors, or tumors that touch the optic disc for greater than 3 clock-hours of optic disk circumference.[7,8]

Local tumor resection: This strategy is used mainly for selected ciliary body or anterior choroidal tumors with smaller basal dimensions and greater thickness.[19]

Enucleation: This approach is used when severe intraocular pressure elevation is a factor. It may also be considered with small- and medium-sized melanomas that are invading the tissues of the optic nerve.[20]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with ciliary body and choroid melanoma, small size. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Medium and Large Choroidal Melanoma

Eye-sparing radiation therapy, either by plaque brachytherapy or external beam, is the preferred option for most patients with medium-sized choroidal melanoma. Enucleation remains the standard therapy for large, choroidal melanomas and melanomas that cause severe glaucoma or invade the optic nerve.

Standard treatment options:

Tumor growth pattern is a factor in the therapeutic decision. If there is a diffuse melanoma or if there is extraocular extension, enucleation should be considered, but radiation therapy can be employed for less extensive disease.

Enucleation. This approach is considered primarily for diffuse melanomas or for cases in which there is extraocular extension; radiation complications or tumor recurrence may sometimes make enucleation necessary.[10]

Large choroidal melanomas

Enucleation when the tumor is judged to be too large for eye-sparing approaches.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with ciliary body and choroid melanoma, medium/large size. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Extraocular Extension and Metastatic Intraocular Melanoma

Extrascleral extension confers a poor prognosis. For patients with gross tumor involvement of the orbit, treatment requires orbital exenteration. However, there is no evidence that such radical surgery will prolong life. Most patients with localized or encapsulated extraocular extension are not exenterated. This subject is controversial.[1-5]

No effective method of systemic treatment has been identified for patients with metastatic ocular melanoma. Available clinical trials should be considered as an option for these patients.

Recurrent Intraocular Melanoma

The prognosis for any patient with recurring or relapsing disease is poor, regardless of cell type or stage. The question and selection of further treatment depends on many factors, including the extent of the lesion, age and health of the patient, prior treatment, and site of recurrence, as well as individual patient considerations. Surgical resection of metastases diagnosed subsequent to initial management of ocular melanoma in single-center, case series of highly selected patients has been reported. The extent to which the occasional favorable outcomes are the result of strong selection factors is not clear, so this approach cannot be considered standard.[1]

Clinical trials are appropriate, and eligible patients should be advised to consider participation in them whenever possible.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent intraocular melanoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of intraocular melanoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

be discussed at a meeting,

be cited with text, or

replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewer for Intraocular (Uveal) Melanoma Treatment is:

Franco M. Muggia, MD (New York University Medical Center)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”

Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.

Contact Us

More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site’s Contact Form.

Get More Information From NCI

Call 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.

Chat online

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

Write to us

For more information from the NCI, please write to this address:

NCI Public Inquiries Office

9609 Medical Center Dr.

Room 2E532 MSC 9760

Bethesda, MD 20892-9760

Search the NCI Web site

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).